US20150073055A1 - Use of modafinil in the treatment of cocaine addicts - Google Patents
Use of modafinil in the treatment of cocaine addicts Download PDFInfo
- Publication number
- US20150073055A1 US20150073055A1 US14/381,896 US201314381896A US2015073055A1 US 20150073055 A1 US20150073055 A1 US 20150073055A1 US 201314381896 A US201314381896 A US 201314381896A US 2015073055 A1 US2015073055 A1 US 2015073055A1
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- US
- United States
- Prior art keywords
- modafinil
- application according
- pharmaceutical composition
- cocaine
- less
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 229960001165 modafinil Drugs 0.000 title claims abstract description 51
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 title claims abstract description 32
- 229960003920 cocaine Drugs 0.000 title claims abstract description 16
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 230000000694 effects Effects 0.000 claims abstract description 9
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- 208000022497 Cocaine-Related disease Diseases 0.000 abstract description 7
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- 238000003756 stirring Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000032140 Sleepiness Diseases 0.000 description 3
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
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- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
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- 206010022437 insomnia Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 206010010219 Compulsions Diseases 0.000 description 1
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
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- 229920003081 Povidone K 30 Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
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- 230000001800 adrenalinergic effect Effects 0.000 description 1
- SEIGJEJVIMIXIU-UHFFFAOYSA-J aluminum;sodium;carbonate;dihydroxide Chemical compound [Na+].O[Al+]O.[O-]C([O-])=O SEIGJEJVIMIXIU-UHFFFAOYSA-J 0.000 description 1
- -1 benzhydryl sulfonyl Chemical class 0.000 description 1
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- 229960002563 disulfiram Drugs 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
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- 230000002474 noradrenergic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
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- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940117394 provigil Drugs 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 230000002582 psychostimulating effect Effects 0.000 description 1
- 238000001671 psychotherapy Methods 0.000 description 1
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- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
Definitions
- Modafinil is 2-[(diphenylmethyl)sulfinyl]acetamide, the molecular formula of which is C 15 H 15 NO 2 S and the structural formula is:
- Modafinil is a wakening drug which has been used in Europe since the nineties: it increases the wakening and diurnal alertness levels and is prescribed in the treatment of narcolepsy.
- the mode of action is not entirely known but it occurs on adrenergic and glutamatergic transmissions. It binds to dopamine carriers and reduces its recapture.
- Modafinil is marketed under the names of Modiodal, Provigil and Alertec.
- the administered dose varies from a taking of 100 mg to two takings of 200 mg per day; the elimination half-life is of about 14 hours in humans.
- Modafinil is marketed in its racemic form which has a chiral center which in fact is a sulfur atom.
- S dextro-rotatory enantiomer
- R levo-rotatory form
- Both enantiomers have the same pharmacological activity in animals; however, in humans, the enantiomer R has a half-life from 10 to 14 hours, The enantiomer S, as for it, has a half-life from 3 to 4 hours [Bibliographic ref.: Wong et al., J. Clin. Pharmacol., 39:30-40 (1999) ; Wong et al., J. Clin. Pharmacol., 39:281-288 (1999); Robertson et al., Clin. Pharmacokinet., 42:123-137 (2003)].
- the enantiomer R After administration, the enantiomer R would have a greater AUC (area under the curve) than the racemic form and less variability of plasma levels.
- Modafinil is used in the treatment of excessive diurnal somnolence associated with narcolepsy with or without catalepsy. Excessive diurnal somnolence is characterized by difficulty in remaining awake and an increase in falling asleep periods occurring at untimely moments.
- the initial recommended dose is 200 mg daily administered in a single taking in the morning, or in two takings in the morning and at noon depending on the response of the patient. The doses may be increased up to 600 mg for patients having an insufficient response.
- An object of the present invention is to make available to the patient, a novel oral medicinal form of S modafinil having increased bioavailability as compared with the racemic form and a shortened duration of action.
- One of the goals is also to provide a formulation capable of meeting the strong interindividual variability and to therefore make available to the patient a homothetic formulation allowing easy adjustment of the administered dose.
- Another object of the invention is to make available to a patient a therapeutic preparation allowing a very fast therapeutic effect as compared with the racemic form and comparatively with the S enantiomer administered alone.
- Patent application US2004/06532 mentions the use of a pharmaceutical form including between 250 and 450 mg of modafinil per therapeutic taking unit.
- the present invention as for it, relates to pharmaceutical forms of S modafinil dosed with 100 mg of active ingredient, or even less.
- Patent application US2009/0123545 relates an association of modafinil compounds wherein the S enantiomer is in a concentration of more than 50%. These compositions are used for increasing the vigilance, alertness condition, and more globally for increasing the stimulation of the CNS (central nervous system).
- the mentioned pharmaceutical data teach that the S modafinil composition is greater than 80% and that the half-life is less than 4 hours.
- the present invention for its part relates to specifically formulated preparations so as to obtain fast action, of less than or equal to 1 hour, and a short duration of activity, a half-life of less than 2 hours.
- the benefit of the present invention is to have a very fast action while being transient.
- the present invention relates to oral therapeutic forms of S modafinil appearing as tablets, sachets or else in the form of gelatin capsules dosed with between 25 and 200 mg of active ingredient and preferentially from 50 to 100 mg.
- formulations presented here are homothetic and therefore identical regardless of the dosages administered to the patient, which contributes to reducing the strong observed variability.
- Modafinil appears as a crystalline white powder practically insoluble in water and partly soluble in methanol and acetone. The result of this is low bioavailability of modafinil; it is estimated to be about 40%. Indeed, as the solubility of the active ingredient is too low, the absolute bioavailability was not able to be determined.
- compositions described here were specifically developed so as to obtain in vitro very fast dissolution and in every case greater than the one obtained with a marketed form; a discriminating dissolution method was therefore specifically developed and allowed selection of the excipients and of the manufacturing methods.
- a method for a novel formulation being the object of the present invention uses the technology of supercritical CO 2 based on the solvent power of CO 2 which may be modulated at will according to the pressure and temperature conditions which are applied to it.
- CO 2 In the supercritical state (more than 74 bars and 31° C.), CO 2 has very particular properties.
- the obtained fluid is characterized by great diffusivity (of the order of that of gases), which gives it good diffusion capability, and a high density which provides it with significant transport and extraction capability.
- a supercritical fluid has another advantage over other solvents: its solubility changes depending on whether its temperature or its pressure is varied. Thus it is possible to ensure that it is a solvent for certain substances at a given instant, and no longer for one at the following instant. This facilitates recovery of the substance which was dissolved.
- the following step consists of spraying the dissolved active ingredient on an inert support, and then of studying the grain size of the obtained particles as well as the crystalline form of the same particles.
- the preparations obtained previously were formulated so as to obtain tablets dosed with 2 mg of S modafinil, these tablets being intended to be administered to the rat during a pharmacokinetic study.
- the method used is the following:
- the method for manufacturing the formulation 1 will now be given, it being understood that the other formulations follow the same method, i.e. weighing the raw materials and double milling of the active ingredients (like for tablets), dispersion of the obtained powder in the excipients and distribution as gelatin capsules.
- This dispersion will be incorporated into the semi-solid gelatin capsule of the HIBAR type and maintained with stirring at 200 rpm by means of stirrer provided with a marine propeller, in order to carry out the filling of the gelatin capsules.
- the temperature of the hopper and of the injector will be adjusted to 27° C. It will then be proceeded with the closing of the gelatin capsules and with their stabilization.
- the one based on ASB has slower dissolution than the three ASC formulations for which the dissolution profiles are identical.
- This double feature in terms of very fast release and transient effect is particularly of interest in the treatment of cocaine addicts.
- the treatment moreover is limited to non-specific psychotropic drugs during detoxification and various psychotherapies with non-proven effectiveness are carried out between these detoxification periods.
- cocaine inhibits neuronal membrane carriers of dopamine (DA) and thus amplifies dopaminergic reactions.
- DA dopamine
- Modafinil is a non-amphetamic psychostimulating drug, for which the mechanism of action is incompletely known but has a major dopaminergic component, specifically at the DATs. Its other noradrenergic and glutamatergic effects are also linked to non-dopaminergic actions of cocaine.
- the goal is to obtain a beginning of very fast action within 15 to 30 minutes allowing the craving window to be reduced and to allow the subject to resist to addictive compulsion.
- the obtained product achieves a much more performing substitution than that of the native molecule.
- the pharmaceutical form according to the invention results in a pharmacokinetic profile which allows this double requirement to be met: a very fast onset of action and a limited wakening effect of S modafinil, of less than 4 hours and preferentially less than 2 hours, in order to avoid the risk of insomnia linked to the prolonged wakening action of R modafinil. Indeed, covering the evening period, one of the sensitive instants for cravings and relapses, requires the product to be taken at the end of the afternoon. Therefore, there will not be any inconvenience in that the patient takes a dose of composition according to the invention at this time of the day. Said pharmaceutical form therefore is actually a therapeutic substitution form for cocaine addicts; it will appear in non-aqueous form, i.e. in solid or semi-solid form, each unit dose will contain from 25 to 200 mg of S modafinil, and preferentially from 50 to 100 mg.
- the pharmaceutical form according to the invention will appear in an oral form, for example tablets or gelatin capsules, thereby avoiding the health risks related to administrations via injections.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Addiction (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Psychiatry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1200581A FR2987267B1 (fr) | 2012-02-28 | 2012-02-28 | Application du modafinil dans le traitement de substitution des cacainomanes |
| FR12/00581 | 2012-02-28 | ||
| PCT/FR2013/000052 WO2013128088A1 (fr) | 2012-02-28 | 2013-02-25 | Application du modafinil dans le traitement des cocaïnomanes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20150073055A1 true US20150073055A1 (en) | 2015-03-12 |
Family
ID=48083447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| US14/381,896 Abandoned US20150073055A1 (en) | 2012-02-28 | 2013-02-25 | Use of modafinil in the treatment of cocaine addicts |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105055404B (zh) * | 2015-08-19 | 2017-07-18 | 四川大学 | Hmgcs2抑制剂在制备治疗可卡因成瘾的药物中的用途 |
| CN105055412B (zh) * | 2015-08-20 | 2018-06-19 | 四川大学 | Nampt抑制剂在制备治疗可卡因成瘾的药物中的用途 |
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|---|---|---|---|---|
| US5618845A (en) * | 1994-10-06 | 1997-04-08 | Cephalon, Inc. | Acetamide derivative having defined particle size |
| FR2771004B1 (fr) | 1997-11-19 | 2000-02-18 | Inst Curie | Utilisation de derives de benzhydryl sulfinyle pour la fabrication de medicaments ayant un effet eveillant dans des situations de troubles de la vigilance d'origine medicamenteuse |
| US20010034373A1 (en) | 2000-02-09 | 2001-10-25 | Matthew Miller | Low dose modafinil for enhancement of cognitive function |
| ES2317943T3 (es) * | 2000-10-11 | 2009-05-01 | Cephalon, Inc. | Composiciones que comprenden compuestos de modafinilo. |
| US20040006532A1 (en) | 2001-03-20 | 2004-01-08 | David Lawrence | Network access risk management |
| US20060024370A1 (en) * | 2004-07-29 | 2006-02-02 | Cephalon France | Modafinil oral lyophilizate |
| US7093476B2 (en) | 2004-09-15 | 2006-08-22 | Ut-Battelle, Llc | Method for fabricating thin californium-containing radioactive source wires |
| US20090123545A1 (en) * | 2005-07-21 | 2009-05-14 | Ron Eyal S | Rapid Onset and Short Term Modafinil Compositions and Methods of Use Thereof |
| JP2009543803A (ja) * | 2006-07-12 | 2009-12-10 | エラン・ファルマ・インターナショナル・リミテッド | モダフィニルのナノ粒子製剤 |
| EP1980240A1 (en) * | 2007-04-11 | 2008-10-15 | Cephalon France | Lyophilized pharmaceutical compositions and methods of making and using same |
| US8173169B2 (en) * | 2007-07-11 | 2012-05-08 | Hikma Pharmaceuticals | Formulation and process for the preparation of modafinil |
-
2012
- 2012-02-28 FR FR1200581A patent/FR2987267B1/fr not_active Expired - Fee Related
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2013
- 2013-02-25 KR KR1020147023180A patent/KR101897855B1/ko not_active Expired - Fee Related
- 2013-02-25 MX MX2014010237A patent/MX348222B/es active IP Right Grant
- 2013-02-25 AU AU2013224831A patent/AU2013224831B2/en not_active Ceased
- 2013-02-25 WO PCT/FR2013/000052 patent/WO2013128088A1/fr active Application Filing
- 2013-02-25 ES ES13715263.3T patent/ES2593276T3/es active Active
- 2013-02-25 HU HUE13715263A patent/HUE030737T2/en unknown
- 2013-02-25 IN IN7831DEN2014 patent/IN2014DN07831A/en unknown
- 2013-02-25 PL PL13715263T patent/PL2819655T3/pl unknown
- 2013-02-25 SG SG11201405316WA patent/SG11201405316WA/en unknown
- 2013-02-25 SI SI201330319A patent/SI2819655T1/sl unknown
- 2013-02-25 JP JP2014559270A patent/JP6163169B2/ja not_active Expired - Fee Related
- 2013-02-25 US US14/381,896 patent/US20150073055A1/en not_active Abandoned
- 2013-02-25 NZ NZ628009A patent/NZ628009A/en not_active IP Right Cessation
- 2013-02-25 HR HRP20161165TT patent/HRP20161165T1/hr unknown
- 2013-02-25 PT PT137152633T patent/PT2819655T/pt unknown
- 2013-02-25 CN CN201380011342.7A patent/CN104159575B/zh not_active Expired - Fee Related
- 2013-02-25 UA UAA201409664A patent/UA113301C2/uk unknown
- 2013-02-25 DK DK13715263.3T patent/DK2819655T3/en active
- 2013-02-25 RS RS20160882A patent/RS55238B1/sr unknown
- 2013-02-25 EP EP13715263.3A patent/EP2819655B1/fr active Active
- 2013-02-25 EA EA201400960A patent/EA025692B1/ru not_active IP Right Cessation
- 2013-02-25 CA CA2863159A patent/CA2863159C/fr not_active Expired - Fee Related
- 2013-02-25 BR BR112014020626A patent/BR112014020626A2/pt not_active Application Discontinuation
- 2013-02-25 LT LTEP13715263.3T patent/LT2819655T/lt unknown
- 2013-02-27 AR ARP130100596A patent/AR090169A1/es unknown
- 2013-02-27 TW TW102106817A patent/TWI626042B/zh not_active IP Right Cessation
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2014
- 2014-08-07 IL IL234009A patent/IL234009B/en active IP Right Grant
- 2014-08-12 ZA ZA2014/05910A patent/ZA201405910B/en unknown
- 2014-08-14 PH PH12014501837A patent/PH12014501837A1/en unknown
- 2014-08-19 CL CL2014002203A patent/CL2014002203A1/es unknown
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2016
- 2016-10-12 SM SM201600363T patent/SMT201600363B/it unknown
- 2016-10-26 CY CY20161101079T patent/CY1118166T1/el unknown
Non-Patent Citations (1)
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| Yeo et al. (âFormation of polymer particles with supercritical fluids: A reviewâ J. of Supercritical Fluids, 34, 2005, 287-308) * |
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